Bacterial gastroenteritis continues to be a highly prevalent disease problem which is particularly severe in malnourished populations. Effective vaccines are not available, and antimicrobial therapy has become more difficult with spread of R-factor mediated resistance among the enteric pathogens. Vaccine development most rationally follows thorough understanding of pathogenesis. Two major virulence mechanisms have been defined for bacterial enteritis: mucosal invasion by intact bacteria and exo-enterotoxin production by non-invasive species. Shigellosis is characterized by invasion however the virulent strain, S. dysenteriae 1, also makes a potent enterotoxin. In model cell culture systems, sensitive cells possess a surface receptor for the toxin. Binding appears to be followed by transport of toxin into the cell by energy dependent pinocytosis, whereas resistant cells do not bind toxin. Preliminary studies of the toxin receptor suggest that it is a glycoprotein containing Beta 1-4 N-acetylglucosamine residues. This study will be aimed at identification and characterization of the receptor in cell culture systems and in intestinal epithelial cells from small and large bowel. Purification of toxin and tracer labeling will be employed to study the kinetics of toxin binding and transport, and to localize the site of action. Biochemical studies will be performed to determine the nature of the toxin effect on these various cells employing both cell isolation and subcellular fractionation techniques as well as organ culture methods. Preliminary studies have failed to indicate an effect on the adenyl cyclase-cyclic AMP mediated secretory mechanism involved in the response to cholera and Escherichia coli enterotoxins. This study will seek to determine whether there is a reciprocal relationship between toxin binding to the intestinal epithelial cell and bacterial invasion in small and large bowel respectively. Bacterial invasion may circumvent the possible lack of the proper surface receptor in colon by delivering toxin directly to the intracellular locus of action.